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Molecular and Human Genetics

Houston, Texas

Department of Molecular and Human Genetics
Department of Molecular and Human Genetics
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Lee-Jun C. Wong, Ph.D.

Lee-Jun C. Wong, Ph.D.

Professor of Molecular and Human Genetics

Other Positions

Director, Mitochondrial Laboratory, BCM Medical Genetics Laboratories
Professor, Program in Translational Biology & Molecular Medicine


B.S., National Taiwan University, 1971
Ph.D., Ohio State University, 1975
Postdoc, Princeton University, 1976

Research Interests

My primary research interest lies in the understanding of mitochondrial genetics and function in disease, cancer, and aging. For many years, our laboratory has had its major contribution to the improvement of the molecular diagnosis of the complex dual genome mitochondrial disorders. This includes the development of quick mutation screen methods, quantification of heteroplasmic mtDNA mutations, sequence analyses, as well as detection of copy number changes in both mitochondrial and nuclear genomes. We developed a dense oligonucleotide array CGH (MitoMet array) targeted to coding exons of genes related to mitochondrial and metabolic disorders for the detection of nuclear and mtDNA deletions. More recently, using one pair of back-to-back primers to amplify the intact circular mitochondrial genome followed by deep massively parallel sequencing, we were able to detect and accurately quantify mtDNA point mutations at any nucleotide positions of the mitochondrial genome. In addition, the breakpoints of mtDNA single and multiple deletions can be unequivocally determined. Using target gene capture and deep next generation sequencing (NGS) technology, we have validated a series of NGS-based panel testing for clinical diagnostic utilities. These include groups of genes involved in specific metabolic pathways, such as glycogen storage disease (GSD) and congenital disorders of glycosylation (CDG); disease with defined clinical phenotype (eg Usher syndrome); genetically heterogeneous diseases involved a particular organ (eg eye, bone); and genetically and clinically heterogeneous mitochondrial disorder. Due to the deep and complete coverage of the sequences, it is possible to detect point mutations and exonic deletions simultaneously using the same set of NGS sequence data.

Reprogramming of energy metabolism is one of the hallmarks of cancer. In proliferating cancer cells, the rates of glycolysis, lactate production, and biosynthesis of lipids and other macromolecules are increased. This Warburg effect is attributed to defective mitochondrial oxidative phosphorylation in cancer cells. Direct evidence for the role of bioenergetics in cancer comes from the occurrence of pathogenic mutations in energy metabolic genes, including succinate dehydrogenase (SDH), a component (complex II) of the mitochondrial respiratory chain, which acts as a tumor suppressor and an oxygen sensor. In the past decade, numerous somatic mitochondrial DNA (mtDNA) alterations have been identified in almost all types of cancers. My research interest is to investigate the mechanism of interplay between the nuclear and mitochondrial genomes and to identify key modulators in the dual genome cross-talk that impact cellular energetics. We established transmitochondrial cybrids with a defined nuclear background containing mitochondria derived from cancer cell lines with various degrees of tumorigenicity and metastatic potency to investigate the functional effect of cancer mitochondria on nuclear gene expression and to provide insight into the mechanism of mitochondrial-nuclear cross-talk as well as the relationship between energy metabolism and cancer development.

In addition to somatic mtDNA changes in tumor cells, germline mtDNA variations and haplogroups may be modifying factors for cancer predisposition and/or metabolic syndromes. We are applying the next generation deep sequencing technology to investigate the intact mitochondrial genome as a whole for low heteroplasmic changes and mtDNA multiple deletions.

Selected Publications

  1. Mitochondrial disorders caused by nuclear genes. Wong, Lee-Jun C. New York: Springer, 2013. NLM ID: 101600018 [Book]
  2. Gai X, Ghezzi D, Johnson MA, Biagosch CA, Shamseldin HE, Haack TB, Reyes A, Tsukikawa M, Sheldon CA, Srinivasan S, Gorza M, Kremer LS, Wieland T, Strom TM, Polyak E, Place E, Consugar M, Ostrovsky J, Vidoni S, Robinson AJ, Wong LJ, Sondheimer N, Salih MA, Al-Jishi E, Raab CP, Bean C, Furlan F, Parini R, Lamperti C, Mayr JA, Konstantopoulou V, Huemer M, Pierce EA, Meitinger T, Freisinger P, Sperl W, Prokisch H, Alkuraya FS, Falk MJ, Zeviani M (2013). Mutations in FBXL4, Encoding a Mitochondrial Protein, Cause Early-Onset Mitochondrial Encephalomyopathy. Am. J. Hum. Genet. 93(3): 482-95. PubMed PMID: 23993194
  3. Wong LJ (2013). Next generation molecular diagnosis of mitochondrial disorders. Mitochondrion 13(4): 379-87. PubMed PMID: 23473862
  4. Kaipparettu BA, Ma Y, Park JH, Lee TL, Zhang Y, Yotnda P, Creighton CJ, Chan WY, Wong LJ (2013). Crosstalk from non-cancerous mitochondria can inhibit tumor properties of metastatic cells by suppressing oncogenic pathways. PLoS One 8(5): e61747. PubMed PMID: 23671572
  5. Tang S, Wang J, Zhang VW, Li FY, Landsverk M, Cui H, Truong CK, Wang G, Chen LC, Graham B, Scaglia F, Schmitt ES, Craigen WJ, Wong LJ (2013). Transition to next generation analysis of the whole mitochondrial genome: a summary of molecular defects. Hum. Mutat. 34(6): 882-93. PubMed PMID: 23463613
  6. Cui H, Li F, Chen D, Wang G, Truong CK, Enns GM, Graham B, Milone M, Landsverk ML, Wang J, Zhang W, Wong LJ (2013). Comprehensive next-generation sequence analyses of the entire mitochondrial genome reveal new insights into the molecular diagnosis of mitochondrial DNA disorders. Genet. Med. 15(5): 388-94. PubMed PMID: 23288206
  7. Wang J, Cui H, Lee NC, Hwu WL, Chien YH, Craigen WJ, Wong LJ, Zhang VW (2013). Clinical application of massively parallel sequencing in the molecular diagnosis of glycogen storage diseases of genetically heterogeneous origin. Genet. Med. 15(2): 106-14. PubMed PMID: 22899091
  8. Zhang W, Cui H, Wong LJ (2012). Comprehensive one-step molecular analyses of mitochondrial genome by massively parallel sequencing. Clin. Chem. 58(9): 1322-31. PubMed PMID: 22777720
  9. Landsverk ML, Douglas GV, Tang S, Zhang VW, Wang GL, Wang J, Wong LJ (2012). Diagnostic approaches to apparent homozygosity. Genet. Med. 14(10): 877-82. PubMed PMID: 22595940
  10. Lee IC, El-Hattab AW, Wang J, Li FY, Weng SW, Craigen WJ, Wong LJ (2012). SURF1-associated Leigh syndrome: a case series and novel mutations. Hum. Mutat. 33(8): 1192-200. PubMed PMID: 22488715
  11. Milone M, Benarroch EE, Wong LJ (2011). POLG-related disorders: defects of the nuclear and mitochondrial genome interaction. Neurology 77(20): 1847-52. PubMed PMID: 22084276
  12. Tang S, Wang J, Lee NC, Milone M, Li Y, Halberg M, Schmitt ES, Craigen WJ, Zhang W, Wong LJ (2011). Mitochondrial DNA polymerase gamma mutations: an ever expanding molecular and clinical spectrum. J. Med. Genet. 48(10): 669-81. PubMed PMID: 21880868

Contact Information

Lee-Jun C. Wong, Ph.D.
Director, Mitochondrial Laboratory
Medical Genetics Laboratories
Baylor College of Medicine
One Baylor Plaza, NAB 2015
Houston, TX, 77030, U.S.A.

Phone: 713-798-1940
Fax: 713-798-8937

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